Nicotine in tobacco product aerosols: 'It's déjà vu all over again'.

First-generation e-liquids have α fb ≈ 1. At cigarette-like total nicotine concentration (Nictot) values of ~60 mg/mL, e-liquid aerosol droplets with α fb≈ 1 are harsh upon inhalation. The design evolution for e-liquids has paralleled that for smoked tobacco, giving a 'déjà vu' trajectory for α fb. For 17th-century 'air-cured' tobacco, α fb in the smoke particles was likely ≥ 0.5. The product α fbNictot in the smoke particles was high. 'Flue-curing' retains higher levels of leaf sugars, which are precursors for organic acids in tobacco smoke, resulting in α fb ≈ 0.02 and lowered harshness. Some tobacco cigarette formulations/designs have been adjusted to restore some nicotine sensory 'kick/impact' with α fb≈ 0.1, as for Marlboro. Overall, for tobacco smoke, the de-freebasing trajectory was α fb ≥ 0.5 → ~0 →~0.1, as compared with α fb= ~1 →~0.1 for e-cigarettes. For JUUL, the result has been, perhaps, an optimised, flavoured nicotine delivery system. The design evolution for e-cigarettes has made them more effective as substitutes to get smokers off combustibles. However, this evolution has likely made e-cigarette products vastly more addictive for never-smokers.